During the First World War, Handley Page produced a series of heavy bombers for the Royal Navy to bomb the German Zeppelin yards, with the ultimate intent of bombing Berlin in revenge for the Zeppelin attacks on London. Handley Page had been asked by the Admiralty to produce a "bloody paralyser of an aeroplane". These aircraft included the O/100 of 1915, the O/400 of 1918 and the four-engined V/1500 with the range to reach Berlin. The V/1500 had only just entered operational service as the war ended in 1918.

In the immediate postwar years, Handley Page modified a number of O/400's to passenger use, which they flew on the London-Paris route as Handley Page Transport. The V/1500 was considered too large to be practical at the time, but a number of design features of the V/1500 were later incorporated into an O/400 airframe to produce their first dedicated passenger design, the W.8. In 1924 Handley Page Transport merged with two other regional airlines to create Imperial Airways, the UK's first national airline service. Handley Page developed several large biplane airliners, including the luxurious Handley Page H.P.42, for use on Imperial routes to Africa and India.

Handley Page developed the Handley Page Slat (or slot, see slats), an auxiliary airfoil mounted ahead and over the main wing, which formed a narrow opening running along the leading edge of the wing to improve airflow at high angles of attack.[4] The leading edge slat was simultaneously designed by the German aerodynamicist Gustav Lachmann, who was later employed by Handley Page. The design was so successful that licensing fees to other companies was their main source of income in the early 1920s.

In 1929, the Cricklewood Aerodrome was closed and a new one built at Radlett, where most aircraft were now to be constructed. However the construction of aircraft at Cricklewood continued until 1964 when the premises were sold to become the Cricklewood trading estate.

With the Second World War looming, Handley Page turned back to bomber design and produced the HP.52 Hampden, which took part in the first British raid on Berlin. In response to a 1936 government request for heavier, longer ranged aircraft, Handley Page tendered the HP.56 design powered by twin Rolls-Royce Vultures and this was ordered, along with what became the Avro Manchester. However the Vulture proved so troublesome that – years before the engine was abandoned by Rolls-Royce in 1940 – the Air Staff decided that the HP.56 should be fitted with four engines instead. Therefore, before reaching prototype stage, the HP.56 design was reworked into the four-engined HP.57 Halifax.[5] The Halifax became the second most prolific British heavy bomber of the war after the Avro Lancaster (itself essentially a four-engine development of the Manchester). Although in some respects (such as crew survivability) better than the Lancaster, the Halifax suffered in terms of altitude performance[6] and was redeployed toward the end of the war as a heavy transport and glider tug, with several variants being specifically built as such, including the HP.70 Halton.

After the war, the British Government sought tenders for jet bombers to carry the nation's nuclear deterrent. The three types produced were known as the V-Bombers, and Handley Page's contribution was the HP.80 Victor, a four-engined, crescent-winged design. This aircraft remained in service (as a tanker aircraft) well beyond the demise of the company which created it.

In 1947 Handley Page bought some of the assets of the bankrupt Miles Aircraft company. These assets include existing designs, tools and jigs, most notably for the Miles M.52 supersonic research aircraft, and the Miles site at Woodley, near Reading. The whole operation was Handley Page (Reading) Ltd, the company constituted to buy and operate the assets formed out of the legally alive but otherwise inactive Handley Page Transport Ltd. The most significant of the inherited designs was the Herald airliner. Designs coming out of the Reading site were shown by the initials HPR (from "Handley Page (Reading) Limited")

Unlike other large British aircraft manufacturers, Handley Page resisted the government's pressure to merge into larger entities. By the late 1960s, the British aviation industry was dominated by just two combines; Hawker Siddeley and the British Aircraft Corporation.

Unable to compete for government orders or with large commercial aircraft, Handley Page produced its final notable Handley Page design; the Jetstream. This was a small turboprop-powered commuter aircraft, with a pressurised cabin and a passenger capacity of 12 to 18. It was designed primarily for the United States "feederliner" market.

The Jetstream was too late to save Handley Page, and the company went into voluntary liquidation in March 1970 and was wound up after 61 years trading under the same name. The Jetstream however lived on as a successful product, the design being purchased and produced by Scottish Aviation at Prestwick, continuing after the company was merged into British Aerospace from 1977.

Radlett Aerodrome was opened in 1929 as a grass aerodrome for Handley Page Civil Aircraft. Its runway was extended in 1939 to enable production of Halifax bombers. By the time of its closure the airfield had two runways:

03/21 approximately 7,000 feet (2,100 m)

15/33 approximately 2,500 feet (760 m)

Most of the towers, hangars and runways were demolished in the 1970s after the Company was terminated. The M25 Motorway now runs on the south side of the site, with Lafarge Aggregates now owning the remainder. The runway surface was removed and replaced with grass, but a shadow remains when viewed from the air.

Handley Page originally used a letter progression to designate types (i.e. R, S, T etc. ) in combination with a number, that may or may not have been meaningful, to designate sub-types (e.g. the O/100 indicated the type's 100 foot wingspan). In 1924, the company began using the letters HP and a number to indicate the model. Thus the O/400 became the HP.16 and the W.8 the HP.18. When the assets of Miles Aircraft were taken over, the latter's Reading design office began using HPR. (for Handley Page Reading), followed by a number (e.g. the HPR.1 Marathon).